Poster Presentation COSA 2015 ASM

Predictive value of de novo and induced epithelial-mesenchymal transition in locally advanced breast cancer treated with neoadjuvant chemotherapy (#179)

Erik W Thompson 1 2 3 , Sally A McLaren 4 , Vijani Dissanayake 1 , Andrew Redfern 5 , Arlene Chan 6 , Alexander Dobrovic 7 , Lilian Soon 8 , Christobel M Saunders 4 9
  1. St. Vincent’s Institute, Melbourne, Australia
  2. Department of Surgery, St. Vincent’s Hospital, University of Melbourne, Melbourne, VIC, Australia
  3. Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia
  4. School of Surgery, University of Western Australia, Perth, WA, Australia
  5. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
  6. Breast Cancer Research Centre - WA , Curtin University, Perth, WA, Australia
  7. School of Cancer Medicine, Olivia Newton-John Cancer Research Institute; La Trobe University, Melbourne, VIC, Australia
  8. Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, University of Sydney, Sydney, NSW , Australia
  9. The Bendat Family Comprehensive Cancer Centre, St John of God HealthCare, Subiaco, WA, Australia

We have characterized epithelial-mesenchymal transition (EMT) status in tissues from 35 locally advanced breast cancer (LABC) patients before and after receiving anthracycline and taxane-based neoadjuvant chemotherapy (NAC). Resected tissue following NAC was available from 17 cases with residual disease. Tissue sections were stained for the epithelial marker cytokeratin 19 (CK19) and the mesenchymal marker vimentin (VIM). Fluorescent, multi-channel microscopy identified co-localization of CK19 and VIM within tumour cells, indicating the presence of EMT.
Evidence of EMT prior to NAC was seen in 14/35 (40%) of LABC cases. There was no association between EMT status pre-NAC and pCR which was observed in 2/14 EMT positive and 4/21 EMT negative patients. However, in patients with detectable EMT pre-NAC there was significantly improved five year disease-free survival (86 vs. 52%, p=0.04) and a trend to improved five year overall survival (86 vs. 62%, p=0.12).
In contrast to pre-NAC EMT, induction of EMT following NAC was associated with trends to worse five year disease-free and overall survival (45 v 75%, p=0.20) and (56 v 75%, p=0.40). Additionally, when events past five years are included in analysis, detectable EMT in the post-NAC tissue sample (induced and retained) correlated with a trend to increased recurrence (p=0.09) and to a statistically significant increase in overall mortality (p=0.04).
This is the first study to explore EMT induction and loss during NAC in the clinical setting. Although patient numbers are few, the data show EMT induction during chemotherapy in a moderate proportion of cases. Observations of significantly superior five year disease free survival in patients without detectable EMT pre-NAC and significantly inferior overall survival in those with visible EMT post-NAC need to be interpreted with caution. Larger studies are needed to further examine this potential prognostic differential between EMT detectable either before or after NAC, and to explore how this may guide therapy.
This work was supported by the EMPathy Breast Cancer Network, a National Collaborative Research Program of the National Breast Cancer Foundation